Inclusion criteria (Powers, et al., 2018)

  • Diagnosis of ischemic stroke causing measurable neurological deficit
  • 18 years of age or older
  • Onset of symptoms < 3 hours
  • Includes patients with severe stroke and patients with mild but disabling stroke symptoms
  • Equally effective in patients < 80 and > 80 years of age
  • For select patients with symptom onset 3- to 4.5- hours: 80 years of age or less
  • No history of diabetes mellitus and prior stroke, no current oral anticoagulant use, NIHSS score ≤ 25, no anticoagulants, cerebral imaging showing ischemia involving less than one third of middle cerebral artery (MCA) territory.
  • Blood pressure (BP) that can be lowered safely (< 185/110 mm Hg) with antihypertensive agents.
  • Initial glucose > 50 mg/dL
  • Non-contrast computed tomography (NCCT) showing early mild-moderate ischemic changes.
  • Patients taking mono-antiplatelet therapy or combination therapy (i.e. aspirin and clopidogrel) and patients with end-stage renal disease on hemodialysis and normal aPTT are eligible for therapy.

Contraindications (Powers, et al., 2018)

  • Unclear time and/or unwitnessed symptom onset and last known baseline state > 3 or 4.5 hours.
  • Current or history of intracranial hemorrhage
  • CT scan showing hypoattenuation or hypoperfusion representing irreversible injury
  • Recent (within 3 months) ischemic stroke, severe head trauma, or intracranial/intraspinal surgery
  • Subarachnoid hemorrhage
  • Gastrointestinal (GI) malignancy or GI bleed within 21 days of stroke event
  • Intracranial conditions that may increase the risk of bleeding such as intracranial
    neoplasm, arteriovenous malformation, or aneurysm
  • Coagulopathy: Platelet count < 100,000/mm3, INR > 1.7, aPTT > 40 seconds, or PT > 15 seconds
  • Low molecular weight heparin (LMWH) treatment doses within the previous 24 hours
  • Current use of anticoagulant with INR > 1.7 or PT > 15 seconds
  • Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated laboratory tests
  • Concurrent use of glycoprotein IIb/IIIa receptor inhibitors
  • Infective endocarditis
  • Aortic arch dissection
  • Intra-axial intracranial neoplasm – lesions located within the brain tissue

Dosage and Administration

  • May be administered IV or intra-arterially (intra-arterial administration is an off-label route).
  • May be given to eligible patients even if endovascular therapies (EVTs) are being considered.
  • Consult package insert for complete instructions on medication preparation, reconstitution and administration.

Nursing Considerations

BEFORE administration:

  • Carefully lower blood pressure (BP) to maintain systolic BP < 185 mmHg and diastolic BP < 110 mmHg before initiating fibrinolytic therapy (Powers, et al., 2018).
  • Due to an increased risk of intracranial bleeding, check INR, PTT and blood glucose prior to administration.
  • Assess for exclusion criteria/contraindications.
  • Explain use and administration of the drug to the patient and the family; tell them to report adverse reactions immediately.
  • Admit to the intensive care unit (ICU) for monitoring.

DURING administration:

  • Maintain strict bedrest during treatment.
  • Measure BP and perform neurological assessment every 15 minutes during infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after treatment.
  • Increase frequency of BP measurements if SBP > 180 mm Hg or if DPB > 105 mm Hg; administer antihypertensive as needed to maintain these levels.
  • If any change in neurological status or symptoms occurs, such as severe headache, acute hypertension, nausea or vomiting, or worsening neurological examination, the alteplase administration should be stopped and a CT scan obtained.
  • Avoid invasive procedures and I.M. injections, and perform venipunctures carefully and only as required, avoiding internal jugular and subclavian venous punctures.
  • Closely monitor the patient for internal bleeding and frequently assess all puncture sites.
  • If serious bleeding occurs, stop the alteplase infusion immediately.

AFTER administration:

  • Measure BP and perform neurologic assessment every 15 minutes during infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after treatment. After the initial 24 hours, monitor vital signs, control blood pressure, and perform neurological assessments frequently per your facility’s policy.
  • Maintain BP < 180/105 mmHg for at least 24 hours after treatment.
  • Hold antiplatelet or anticoagulation therapy and invasive procedures for 24 hours following administration.
  • Monitor for serious adverse events, such as bleeding and angioedema.
  • Concomitant use of angiotensin-converting enzyme (ACE) inhibitors may increase the risk of orolingual angioedema.
  • Concomitant use of anticoagulants and drugs that inhibit platelet function increase the risk of bleeding.
  • Delay insertion of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters if patient can be managed without them.
  • Obtain follow-up CT or MRI scan 24 hours after treatment before starting anticoagulants or antiplatelet agents.

Adverse reactions

  • Bleeding (most common)
  • Orolingual angioedema
  • Arrhythmias
  • Hypotension
  • Edema
  • Cholesterol embolization
  • Venous thrombosis
  • Re-embolization of deep venous thrombi (DVT) in patients with pulmonary embolism
  • Nausea
  • Vomiting
  • Hypersensitivity reactions

Management of Symptomatic Bleeding Within 24 Hours After Administration of IV Alteplase (Powers, et al., 2018)

  • Stop alteplase infusion.
  • Obtain CBC, PT (INR), aPTT, fibrinogen level, and type and cross-match.
  • Obtain emergent nonenhanced head CT. Per order, administer cryoprecipitate (includes factor VIII): 10 U infused over 10-30 minutes (onset in 1 hour, peaks in 12 hour); administer additional dose for fibrinogen level < 200 mg/dL.
  • Per order, administer tranexamic acid 1000 mg IV infused over 10 min OR Ɛ-aminocaproic acid 4-5 g over 1 hour, followed by 1 g IV until bleeding is controlled.
  • Obtain hematology and neurosurgery consult.
  • Manage BP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), temperature, and glucose

Management of Orolingual Angioedema Associated with IV Alteplase (Powers, et al., 2018)

  • Maintain airway.
  • Intubation may not be needed if edema is limited to anterior tongue and lips.
  • Edema involving larynx, palate, floor of mouth, oropharynx with rapid progression (within 30 minutes) poses higher risk of respiratory compromise requiring intubation.
  • Awake fiberoptic intubation is preferred.
  • As ordered, perform the following:
  • Discontinue IV alteplase infusion and hold ACE-inhibitors.
  • Administer IV methylprednisolone 125 mg.
  • Administer IV diphenhydramine 50 mg.
  • Administer ranitidine 50 mg IV or famotidine 20 mg IV.
  • If there is an increase in angioedema, administer epinephrine (0.1%) 0.3 mL subcutaneously or by nebulizer 0.5 mL.
  • Administer icatibant (selective bradykinin B2 receptor antagonist), 3 mL (30 mg) subcutaneously in abdomen.